ADCY5-related DyskinesiaADCY5-CAFNCT04469283
Caffeine Efficacy in ADCY5-related Dyskinesia
An observational study of ADCY5-related Dyskinesia, run by Assistance Publique - Hôpitaux de Paris.
Trial summary
Heterozygous mutations in ADCY5 induce hyperactivity of striatal adenylate cyclase type 5 (AC5), manifesting as early-onset hyperkinetic movement disorders. Numerous treatments have been tried without much efficacy thus far. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- ADCY5-related Dyskinesia
- What is being tested?
- caffeine and movement disorders
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- 15 Jul 2020to 15 Jul 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: patients with genetically proven ADCY5-related dyskinesia
Who may be able to join
- Proven genetic diagnosis of ADCY5-related dyskinesia
- Adults or children without age limits
- Past or present caffeine intake
- Non-opposition by the patient (adults) or the legal representatives (minors) in France, and patient information according to each country's legislation in other countries.
- 4.2. Exclusion criteria None.
Who cannot join
None listed.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Study of Caffeine Efficacy in ADCY5-related Dyskinesia - a Retrospective Study
Heterozygous mutations in ADCY5 induce hyperactivity of striatal adenylate cyclase type 5 (AC5), manifesting as early-onset hyperkinetic movement disorders. Numerous treatments have been tried without much efficacy thus far. Two patients from the same family reported efficacy of caffeine on paroxysmal episodes, both to prevent episodes and to reduce their duration (efficacy estimated to be around 80%), which was specific to caffeine as it was reproduced with caffeine citrate capsules. Interestingly, there is a rationale underlying this observation. Indeed, caffeine is an antagonist of adenosine A2A receptors (A2AR), which activate AC5 and are localized preferentially in striatal neurons that express dopamine receptors D2 .Caffeine therefore likely induces AC5 inhibition, and thus clinical improvement in patients with hyperactivity of this protein. This observation has been recently published in2019.
The investigators will collect preliminary data by interviewing our neurologist and neuropediatric colleagues, in France and abroad since it is a rare disease, on the effect of caffeine on motor symptoms and global clinical status in their ADCY5 patients.
Read the detailed description
Heterozygous mutations in ADCY5 induce hyperactivity of striatal adenylate cyclase type 5 (AC5) manifesting as early-onset hyperkinetic movement disorders. The phenotype combines chorea, dystonia and/or myoclonus with frequent facial involvement, axial hypotonia, fluctuations and/or episodes of paroxysmal dyskinesia which can be nocturnal and/or painful, generally without intellectual deficiency, epilepsy or cerebellar syndrome . It is a very rare disease, affecting around twenty patients in France.
Scientific context of the research:
Numerous treatments have been tried without much efficacy thus far.
Scientific justification for the study:
Two patients from the same family reported efficacy of caffeine on paroxysmal episodes, both to prevent episodes and to reduce their duration (efficacy estimated to be around 80%), which was specific to caffeine as it was reproduced with caffeine citrate capsules. Interestingly there is a rationale underlying this situation. Indeed, caffeine is an antagonist of adenosine A2A receptors (A2AR), which activate AC5 and are localized preferentially in striatal neurons that express dopamine receptors D2. Caffeine therefore likely induces inhibition of AC5, and thus clinical improvement in patients with hyperactivity of this protein. This observation has been recently published in 2019 HYPOTHESIS Our hypothesis is that most patients with ADCY5-related dyskinesia respond well to caffeine.
This study is a multicentric retrospective study, which will be conducted in neurology and neuropediatric departments across the world.
Participants will be recruited by their own physician. This research will take place over 18 months in total: 12 month to collect all patients' data and 6 months to analyse data.
The number of participants will be between 5 and 20, depending on colleagues replies.
This research will take place over 18 months in total: 12 month to collect all patients' data and 6 months to analyse data.
- Conditions
- ADCY5-related Dyskinesia
- Being tested
- caffeine and movement disorders
- Keywords
- ADCY5, dyskinesia, caffeine
- Medical subject headings
- Dyskinesia, Familial, with Facial Myokymia, Dyskinesias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
caffeine and movement disordersOther
Caffeine efficacy on movement disorders in patients with ADCY5-related dyskinesia.
| Study group | Role | What they receive |
|---|---|---|
| caffeine efficacy | Collection of preliminary data on caffeine efficacy on movement disorders in patients with ADCY5-related dyskinesia. Receives: Other: caffeine and movement disorders |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of responders to caffeine
the response being defined as an improvement of overall involuntary movements of 40% or more.
Measured: 12 months
Secondary outcomes (3)
Global improvement of involuntary movements,
Global change of involuntary movements ranging from 0 (no change) to 10 (disappearance of involuntary movements)
Measured: 12 MONTHS
Global clinical change
Global clinical change ranging from 0 (no change) to 10 (normalization of the global clinical state)
Measured: 12 months
Duration of paroxysmal episodes of movement disorders
Change of the duration of paroxysmal episodes of movement disorders with caffeine
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2020
- Study start15 Jul 2020 (estimated)
- Primary completion15 Jul 2021 (estimated)
- Study completion15 Jul 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ADCY5-related DyskinesiaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04469283
- Sponsor's protocol ID
- APHP200193
- Acronym
- ADCY5-CAF
- Status last verified
- Jun 2020
- First submitted
- 23 Jun 2020
- Last updated
- 14 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Meneret A, Gras D, McGovern E, Roze E. Caffeine and the Dyskinesia Related to Mutations in the ADCY5 Gene. Ann Intern Med. 2019 Sep 17;171(6):439. doi: 10.7326/L19-0038. Epub 2019 Jun 11. No abstract available.
PubMed 31181574
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Caffeine Efficacy in ADCY5-related Dyskinesia - a Retrospective Study
- ClinicalTrials.gov ID
- NCT04469283
- Acronym / sponsor ID
- ADCY5-CAF / APHP200193
- Conditions
- ADCY5-related Dyskinesia
- Keywords
- ADCY5, dyskinesia, caffeine
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 15 Jul 2020 (estimated)
- Primary completion
- 15 Jul 2021 (estimated)
- Study completion
- 15 Jul 2021 (estimated)
- First posted
- 14 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Heterozygous mutations in ADCY5 induce hyperactivity of striatal adenylate cyclase type 5 (AC5), manifesting as early-onset hyperkinetic movement disorders. Numerous treatments have been tried without much efficacy thus far. Two patients from the same family reported efficacy of caffeine on paroxysmal episodes, both to prevent episodes and to reduce their duration (efficacy estimated to be around 80%), which was specific to caffeine as it was reproduced with caffeine citrate capsules. Interestingly, there is a rationale underlying this observation. Indeed, caffeine is an antagonist of adenosine A2A receptors (A2AR), which activate AC5 and are localized preferentially in striatal neurons that express dopamine receptors D2 .Caffeine therefore likely induces AC5 inhibition, and thus clinical improvement in patients with hyperactivity of this protein. This observation has been recently published in2019.
The investigators will collect preliminary data by interviewing our neurologist and neuropediatric colleagues, in France and abroad since it is a rare disease, on the effect of caffeine on motor symptoms and global clinical status in their ADCY5 patients.
Detailed description
Heterozygous mutations in ADCY5 induce hyperactivity of striatal adenylate cyclase type 5 (AC5) manifesting as early-onset hyperkinetic movement disorders. The phenotype combines chorea, dystonia and/or myoclonus with frequent facial involvement, axial hypotonia, fluctuations and/or episodes of paroxysmal dyskinesia which can be nocturnal and/or painful, generally without intellectual deficiency, epilepsy or cerebellar syndrome . It is a very rare disease, affecting around twenty patients in France.
Scientific context of the research:
Numerous treatments have been tried without much efficacy thus far.
Scientific justification for the study:
Two patients from the same family reported efficacy of caffeine on paroxysmal episodes, both to prevent episodes and to reduce their duration (efficacy estimated to be around 80%), which was specific to caffeine as it was reproduced with caffeine citrate capsules. Interestingly there is a rationale underlying this situation. Indeed, caffeine is an antagonist of adenosine A2A receptors (A2AR), which activate AC5 and are localized preferentially in striatal neurons that express dopamine receptors D2. Caffeine therefore likely induces inhibition of AC5, and thus clinical improvement in patients with hyperactivity of this protein. This observation has been recently published in 2019 HYPOTHESIS Our hypothesis is that most patients with ADCY5-related dyskinesia respond well to caffeine.
This study is a multicentric retrospective study, which will be conducted in neurology and neuropediatric departments across the world.
Participants will be recruited by their own physician. This research will take place over 18 months in total: 12 month to collect all patients' data and 6 months to analyse data.
The number of participants will be between 5 and 20, depending on colleagues replies.
This research will take place over 18 months in total: 12 month to collect all patients' data and 6 months to analyse data.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| caffeine efficacy | – | Other: caffeine and movement disordersCollection of preliminary data on caffeine efficacy on movement disorders in patients with ADCY5-related dyskinesia. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- patients with genetically proven ADCY5-related dyskinesia
Key inclusion criteria (5 listed)
- Proven genetic diagnosis of ADCY5-related dyskinesia
- Adults or children without age limits
- Past or present caffeine intake
- Non-opposition by the patient (adults) or the legal representatives (minors) in France, and patient information according to each country's legislation in other countries.
- 4.2. Exclusion criteria None.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| caffeine and movement disordersCaffeine efficacy on movement disorders in patients with ADCY5-related dyskinesia. | Other | caffeine efficacy |
Primary outcome
Percentage of responders to caffeine
Time frame: 12 months
the response being defined as an improvement of overall involuntary movements of 40% or more.
3 secondary outcomes
Global improvement of involuntary movements,
Time frame: 12 MONTHS
Global clinical change
Time frame: 12 months
Duration of paroxysmal episodes of movement disorders
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2020.
- Background: PubMed 31181574Meneret A, Gras D, McGovern E, Roze E. Caffeine and the Dyskinesia Related to Mutations in the ADCY5 Gene. Ann Intern Med. 2019 Sep 17;171(6):439. doi: 10.7326/L19-0038. Epub 2019 Jun 11. No abstract available.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
An observational study of ADCY5-related Dyskinesia, run by Assistance Publique - Hôpitaux de Paris.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Aurélie MENERET, MD (1 42 16 24 61 ext. +33, aurelie.meneret@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of responders to caffeine (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04469283, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2020.